Multi-omics characterization of RNA binding proteins reveals disease comorbidities and potential drugs in COVID-19.

The COVID-19 has led to a devastating global health crisis, which emphasizes the urgent need to deepen our understanding of the molecular mechanism and identifying potential antiviral drugs. Here, we comprehensively analyzed the transcriptomic and proteomic profiles of 178 COVID-19 patients, ranging from asymptomatic to critically ill. Our analyses found that the RNA binding proteins (RBPs) were likely to be perturbed in infection. Interactome analysis revealed that RBPs interact with virus proteins and the viral interacting RBPs were likely to locate in central regions of human protein-protein interaction network. Functional enrichment analysis revealed that the viral interacting RBPs were likely to be enriched in RNA transport, apoptosis and viral genome replication-related pathways. Based on network proximity analyses of 299 human complex-disease genes and COVID-19-related RBPs in the human interactome, we revealed the significant associations between complex diseases and COVID-19. Network analysis also implicated potential antiviral drugs for treatment of COVID-19. In summary, our integrative characterization of COVID-19 patients may thus help providing evidence regarding pathophysiology and potential therapeutic strategies for COVID-19.

Identification of Monocytes Associated with Severe COVID-19 in the PBMCs of Severely Infected patients Through Single-Cell Transcriptome Sequencing.

Understanding the immunological characteristics of monocytes-including the characteristics associated with fibrosis-in severe coronavirus disease 2019 (COVID-19) is crucial for understanding the pathogenic mechanism of the disease and preventing disease severity. In this study, we performed single-cell transcriptomic sequencing of peripheral blood samples collected from six healthy controls and 14 COVID-19 samples including severe, moderate, and convalescent samples from three severely/critically ill and four moderately ill patients. We found that the monocytes were strongly remodeled in the severely/critically ill patients with COVID-19, with an increased proportion of monocytes and seriously reduced diversity. In addition, we discovered two novel severe-disease-specific monocyte subsets: Mono 0 and Mono 5. These subsets expressed amphiregulin (AREG), epiregulin (EREG), and cytokine interleukin-18 (IL-18) gene, exhibited an enriched erythroblastic leukemia viral oncogene homolog (ErbB) signaling pathway, and appeared to exhibit pro-fibrogenic and pro-inflammation characteristics. We also found metabolic changes in Mono 0 and Mono 5, including increased glycolysis/gluconeogenesis and an increased hypoxia inducible factor-1 (HIF-1) signaling pathway. Notably, one pre-severe sample displayed a monocyte atlas similar to that of the severe/critical samples. In conclusion, our study discovered two novel severe-disease-specific monocyte subsets as potential predictors and therapeutic targets for severe COVID-19. Overall, this study provides potential predictors for severe disease and therapeutic targets for COVID-19 and thus provides a resource for further studies on COVID-19.

Bioaerosol dispersion and environmental risk simulation: Method and a case study for a biopharmaceutical plant of Gansu province, China.

Pathogenic bacteria pose a great threat to global public health from environmental and public health perspectives, especially regarding the impact of the COVID-19 pandemic worldwide. As a result, the increased risk of pathogenic bioaerosol exposure imposes a considerable health burden and raises specific concerns about the layout and location of vaccine manufacturers. This study proposed a grid computing method based on the CALPUFF modelling system and population-based environmental risks to reduce bioaerosol-related potential risks. We previously used the CALPUFF model to quantify the diffusion level, the spatial distribution of emissions, and potential environmental risks of bioaerosol leakage in Gansu province's Zhongmu Lanzhou biopharmaceutical plant from July 24, 2019, to August 20, 2019. By combining it with publicly available test data, the credibility was confirmed. Based on our previous research, the CALPUFF model application combined with the environmental population-based environmental risks in two scenarios: the layout and site selection, was explored by using the leakage accident of Zhongmu Lanzhou biopharmaceutical plant of Gansu province as a case study. Our results showed that the site selection method of scenario 2 coupled with the buffer area was more reasonable than scenario 1, and the final layout site selection point of scenario 2 was grid 157 as the optimal layout point. The simulation results demonstrated agreement with the actual survey. Our findings could assist global bioaerosol manufacturers in developing appropriate layout and site selection strategies to reduce bioaerosol-related potential environmental risks.

Summary and overview of the first ISMRM workshop on magnetic resonance elastography, August 25-26, 2022, Berlin, Germany.

An ISMRM workshop on MR elastography was held at Charité-Universitätsmedizin Berlin on August 25-26, 2022. As an exclusively in-person event, 65 participants from 9 countries attended the workshop despite COVID-19-related restrictions. The topics of the workshop covered cellular and microtissue mechanical interactions, the development of MR elastography driver technology, approaches to inverse problems, clinical applications, and integration of MR elastography into multiparametric MRI protocols. The workshop was a great success by promoting direct knowledge exchange as well as for strategizing future directions for MR elastography. In this symposium review, we briefly summarized all oral presentations as well as the concluding panel discussion.

A TLR7-nanoparticle adjuvant promotes a broad immune response against heterologous strains of influenza and SARS-CoV-2.

The ideal vaccine against viruses such as influenza and SARS-CoV-2 must provide a robust, durable and broad immune protection against multiple viral variants. However, antibody responses to current vaccines often lack robust cross-reactivity. Here we describe a polymeric Toll-like receptor 7 agonist nanoparticle (TLR7-NP) adjuvant, which enhances lymph node targeting, and leads to persistent activation of immune cells and broad immune responses. When mixed with alum-adsorbed antigens, this TLR7-NP adjuvant elicits cross-reactive antibodies for both dominant and subdominant epitopes and antigen-specific CD8+ T-cell responses in mice. This TLR7-NP-adjuvanted influenza subunit vaccine successfully protects mice against viral challenge of a different strain. This strategy also enhances the antibody response to a SARS-CoV-2 subunit vaccine against multiple viral variants that have emerged. Moreover, this TLR7-NP augments antigen-specific responses in human tonsil organoids. Overall, we describe a nanoparticle adjuvant to improve immune responses to viral antigens, with promising implications for developing broadly protective vaccines.

Network analysis of COVID-19-related PTSD and depressive symptoms among Chinese general population and comorbidity subgroup.

OBJECTIVE: Posttraumatic stress disorder (PTSD) and depressive symptoms are prevalent and highly correlated mental health outcomes of traumatic events, but their comorbidity in the COVID-19 pandemic has not been examined with evidence from Chinese culture. METHOD: With information from 2,858 Chinese adults, this study used a network analysis to investigate the relationship between PTSD and depressive symptoms along with their symptoms-structure associations. RESULTS: Results indicated similar positive connections among similar cluster symptoms (i.e., positive affect) in both general and comorbidity-reported populations. Self-destructive/reckless behaviors were core symptoms in the general population, and interpersonal difficulties were core symptoms in the comorbidity subgroup. Finally, the very strong communication seen between "arousal and reactivity alterations" and "depressed affect" deserves more attention. CONCLUSION: Our results indicated interpersonal symptoms can be important targets when intervening or treating PTSD and depressive symptoms related to COVID-19 in the clinical population. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Social support profiles correlate with depressive symptoms among Chinese parents during the COVID-19 pandemic: A latent profile analysis.

This study explored pandemic-related social support profiles and investigated their relationships with depressive symptoms among Chinese parents during the COVID-19 pandemic. The hypotheses were evaluated in an online cross-sectional survey of 1286 parents. Latent profile analysis identified two profiles of received social support (isolated and integrated support). Three convergent profiles (high, moderate, and low support) and one divergent profile were found in perceived social support. The results revealed that the distribution of age, region, income and educational level varied across these profiles. Only the "high" (ß = -0.11, p < 0.01) and "divergent" (ß = -0.12, p < 0.01) profiles of perceived social support were negatively associated with parents' depressive symptoms. These findings highlight the importance of developing better-targeted intervention programs aimed at optimizing the allocation and improving the quantity and quality of supportive resources for parents.

Surface-enhanced Raman scattering as a potential strategy for wearable flexible sensing and point-of-care testing non-invasive medical diagnosis.

As a powerful and effective analytical tool, surface-enhanced Raman scattering (SERS) has attracted considerable research interest in the fields of wearable flexible sensing and non-invasive point-of-care testing (POCT) medical diagnosis. In this mini-review, we briefly summarize the design strategy, the development progress of wearable SERS sensors and its applications in this field. We present SERS substrate analysis of material design requirements for wearable sensors and highlight the benefits of novel plasmonic particle-in-cavity (PIC)-based nanostructures for flexible SERS sensors, as well as the unique interfacial adhesion effect and excellent mechanical properties of natural silk fibroin (SF) derived from natural cocoons, indicating promising futures for applications in the field of flexible electronic, optical, and electrical sensors. Additionally, SERS wearable sensors have shown great potential in the fields of different disease markers as well as in the diagnosis testing for COVID-19. Finally, the current challenges in this field are pointed out, as well as the promising prospects of combining SERS wearable sensors with other portable health monitoring systems for POCT medical diagnosis in the future.

Summary and overview of the first ISMRM workshop on magnetic resonance elastography, August 25-26, 2022, Berlin, Germany.

An ISMRM workshop on MR elastography was held at Charité-Universitätsmedizin Berlin on August 25-26, 2022. As an exclusively in-person event, 65 participants from 9 countries attended the workshop despite COVID-19-related restrictions. The topics of the workshop covered cellular and microtissue mechanical interactions, the development of MR elastography driver technology, approaches to inverse problems, clinical applications, and integration of MR elastography into multiparametric MRI protocols. The workshop was a great success by promoting direct knowledge exchange as well as for strategizing future directions for MR elastography. In this symposium review, we briefly summarized all oral presentations as well as the concluding panel discussion.

The associations of pandemic-related difficulties with depressive symptoms and psychological growth among American older adults: Social support as moderators.

The COVID-19 pandemic brought social, health-related, and financial risks to older adults, yet their associations with depressive symptoms and posttraumatic growth (PTG) were not systematically examined. With 3504 respondents aged 60 and over from Health and Retirement Survey, this study found pandemic-related healthcare delay and financial hardship associated with elevated depressive symptoms and decreased PTG, whereas social disruption predicted greater PTG. When confronted with multidimensional difficulties, a higher level of social support buffered depressive symptoms and enhanced PTG following healthcare delay, while those from immediate family members carried the weighing of moderation. Additionally, the moderation effect varied between support types, as exclusive instrumental support engendered more depressive symptoms and squeezed PTG by stimulating a sense of incompetence for older adults. Inversely, receiving both instrumental and emotional support helped individuals of older age against financial-related depressive symptoms. These findings shed light on older adults' mental health promotion in a pandemic context.

Relationship among Child Maltreatment, Parental Conflict, and Mental Health of Children during the COVID-19 Lockdown in China.

Children are more likely to experience maltreatment and parental conflict in a pandemic context, which can exacerbate their vulnerability to psychological disorders. The purpose of the present study was to examine mental health symptoms in children aged 0 to 10 years and consider related factors from the perspectives of maltreatment and parental conflict during the COVID-19 lockdown. Participants were 1286 parents aged 18 years and over with children aged 0 to 10 years were included. Several multivariable linear regressions were used to analyze the data. The largest variance in child mental health was explained by child maltreatment, as more maltreatment predicted higher reported psychological problems (standardized beta = 0.49, P < 0.001). Comparatively, parental conflict predicted less variance in mental health problems than maltreatment (standardized beta = 0.18, P < 0.001). Children who experienced more maltreatment experience and exposure to COVID-19 showed elevated levels of mental health symptoms (standardized beta = 0.06, p < 0.05), as did those who experienced parental conflict and pandemic exposure (standardized beta = 0.06, p < 0.05). The findings highlight that tailored programs that focus on a healthy family environment and strategic parental support services may be particularly effective in reducing children's mental health problems due to COVID-19 exposure.

Safety and Immunogenicity of an Inactivated COVID-19 Vaccine, WIBP-CorV, in Healthy Children: Interim Analysis of a Randomized, Double-Blind, Controlled, Phase 1/2 Trial.

Safe and effective vaccines against SARS-CoV-2 for children are urgently needed. Here we aimed to assess the safety and immunogenicity of an inactivated COVID-19 vaccine candidate, WIBP-CorV, in participants aged 3-17 years. A randomized, double-blind, placebo-controlled, phase 1/2 clinical trial was conducted in Henan Province, China, in healthy children aged 3-17 years. 240 participants in phase 1 trial and 576 participants in phase 2 trial were randomly assigned to vaccine or control with an age de-escalation in three cohorts (3-5, 6-12 and 13-17 years) and dose-escalation in three groups (2.5, 5.0 and 10.0µg/dose), and received 3 intramuscular injections at day 0, 28, and 56. WIBP-CorV showed a promising safety profile with approximately 17% adverse reactions within 30 days after injection and no grade 3 or worse adverse events. The most common adverse reaction was injection site pain, followed by fever, which were mild and self-limiting. The geometric mean titers of neutralizing antibody ranged from 102.2 to 1065.5 in vaccinated participants at 28 days after the third vaccination, and maintained at a range of 14.3 to 218.2 at day 180 after the third vaccination. WIBP-CorV elicited significantly higher titers of neutralizing antibody in the cohort aged 3-5 years than the other two cohorts. There were no detectable antibody responses in all alum-only groups. Taken together, our data demonstrate that WIBP-CorV is safe and well tolerated at all tested doses in participants aged 3-17 years, and elicited robust humoral responses against SARS-CoV-2 lasted for at least 6 months after the third vaccination. This study is ongoing and is registered with www.chictr.org.cn, ChiCTR2000031809.

Reinfection in patients with COVID-19: a systematic review.

BACKGROUND: With the continuation of the COVID-19 pandemic, some COVID-19 patients have become reinfected with the virus. Viral gene sequencing has found that some of these patients were reinfected by the different and others by same strains. This has raised concerns about the effectiveness of immunity after infection and the reliability of vaccines. To this end, we conducted a systematic review to assess the characteristics of patients with reinfection and possible causes. METHODS: A systematic search was conducted across eight databases: PubMed, Embase, Web of Science, The Cochrane Library, CNKI, WanFang, VIP and SinoMed from December 1, 2019 to September 1, 2021. The quality of included studies were assessed using JBI critical appraisal tools and Newcastle-Ottawa Scale. RESULTS: This study included 50 studies from 20 countries. There were 118 cases of reinfection. Twenty-five patients were reported to have at least one complication. The shortest duration between the first infection and reinfection was 19 days and the longest was 293 days. During the first infection and reinfection, cough (51.6% and 43.9%) and fever (50% and 30.3%) were the most common symptoms respectively. Nine patients recovered, seven patients died, and five patients were hospitalized, but 97 patients' prognosis were unknown. B.1 is the most common variant strain at the first infection. B.1.1.7, B.1.128 and B.1.351 were the most common variant strains at reinfection. Thirty-three patients were infected by different strains and 9 patients were reported as being infected with the same strain. CONCLUSIONS: Our research shows that it is possible for rehabilitated patients to be reinfected by SARS-COV-2. To date, the causes and risk factors of COVID-19 reinfection are not fully understood. For patients with reinfection, the diagnosis and management should be consistent with the treatment of the first infection. The public, including rehabilitated patients, should be fully vaccinated, wear masks in public places, and pay attention to maintaining social distance to avoid reinfection with the virus.

Prevalence and related factors of child posttraumatic stress disorder during COVID-19 pandemic: A systematic review and meta-analysis.

BACKGROUND: The COVID-19 pandemic has drastically impacted many aspects of society and has indirectly produced various psychological consequences. This systematic review aimed to estimate the worldwide prevalence of posttraumatic stress disorder (PTSD) in children due to the COVID-19 pandemic, as well as to identify protective or risk factors contributing to child PTSD. METHODS: We conducted a systematic literature search in the PubMed, ProQuest, PsycINFO, Embase, Web of Science, WanFang, CNKI, and VIP databases. We searched for studies published between January 1, 2020 and May 26, 2021, that reported the prevalence of child PTSD due to the COVID-19 pandemic, as well as factors contributing to child PTSD. Eighteen studies were included in our systematic review, of which 10 studies were included in the meta-analysis. RESULTS: The estimated prevalence of child PTSD after the COVID-19 outbreak was 28.15% (95% CI: 19.46-36.84%, I² = 99.7%). In subgroup analyses for specific regions the estimated prevalence of post-pandemic child PTSD was 19.61% (95% CI: 11.23-27.98%) in China, 50.8% (95% CI: 34.12-67.49%) in the USA, and 50.08% in Italy (95% CI: 47.32-52.84%). CONCLUSIONS: Factors contributing to child PTSD were categorized into four aspects: personal factors, family factors, social factors and infectious diseases related factors. Based on this, we presented a new framework summarizing the occurrence and influence of the COVID-19 related child PTSD, which may contribute to a better understanding, prevention and development of interventions for child PTSD in forthcoming pandemics.

The Combined Impact of Gender and Age on Post-traumatic Stress Symptoms, Depression, and Insomnia During COVID-19 Outbreak in China.

The mental health problems might have been increased owing to the COVID-19 pandemic with the commencement of the year 2020, therefore, an epidemiological survey appraising the burden of mental health issues among the general population is imperative. This cross-sectional study attempts to reveal the underlying mental health conditions, such as Post-Traumatic Stress Symptoms (PTSS), depression, and insomnia, relating to the pandemic situation, and to further examine the combined effects of gender and age on the COVID-19 related mental health consequences. An online survey was conducted among 2,992 adults in China from February 1st 2020 to February 10th 2020. The study uses binary logistic regression to analyze the potential factors associated with PTSD, depression, and insomnia. The results indicate that the prevalence of PTSS, depression, and insomnia are 19.5, 26.9, and 19.6% respectively during the COVID-19. Men and women show different rates of PTSS and depression, whereas no insomnia is found in both males and females. The females above 50 years of age have a lower level of depressive symptoms (OR = 0.448, 95%CI: 0.220-0.911, Cohen's d = -0.443) as compared with females aged 18-25; while the highest effect sizes for PTSS (OR = 2.846, 95%CI: 1.725-4.695, Cohen's d = 0.537) and the depression (OR = 2.024, 95%CI: 1.317-3.111, Cohen's d = 0.314) are seen in males aged 26 to 30. Besides gender, education, living conditions, direct exposure to COVID-19, the post mental and the physical health condition is related to PTSS, depression, and insomnia. Our study suggests that high-risk groups, especially those having two or more related factors and young men, should be the focus of mental health intervention.

Maternal mental health during the COVID-19 lockdown in China, Italy, and the Netherlands: a cross-validation study.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic had brought negative consequences and new stressors to mothers. The current study aims to compare factors predicting maternal mental health during the COVID-19 lockdown in China, Italy, and the Netherlands. METHODS: The sample consisted of 900 Dutch, 641 Italian, and 922 Chinese mothers (age M = 36.74, s.d. = 5.58) who completed an online questionnaire during the lockdown. Ten-fold cross-validation models were applied to explore the predictive performance of related factors for maternal mental health, and also to test similarities and differences between the countries. RESULTS: COVID-19-related stress and family conflict are risk factors and resilience is a protective factor in association with maternal mental health in each country. Despite these shared factors, unique best models were identified for each of the three countries. In Italy, maternal age and poor physical health were related to more mental health symptoms, while in the Netherlands maternal high education and unemployment were associated with mental health symptoms. In China, having more than one child, being married, and grandparental support for mothers were important protective factors lowering the risk for mental health symptoms. Moreover, high SES (mother's high education, high family income) and poor physical health were found to relate to high levels of mental health symptoms among Chinese mothers. CONCLUSIONS: These findings are important for the identification of at-risk mothers and the development of mental health promotion programs during COVID-19 and future pandemics.

Maternal mental health during the COVID-19 lockdown in China, Italy, and the Netherlands: a cross-validation study.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic had brought negative consequences and new stressors to mothers. The current study aims to compare factors predicting maternal mental health during the COVID-19 lockdown in China, Italy, and the Netherlands. METHODS: The sample consisted of 900 Dutch, 641 Italian, and 922 Chinese mothers (age M = 36.74, s.d. = 5.58) who completed an online questionnaire during the lockdown. Ten-fold cross-validation models were applied to explore the predictive performance of related factors for maternal mental health, and also to test similarities and differences between the countries. RESULTS: COVID-19-related stress and family conflict are risk factors and resilience is a protective factor in association with maternal mental health in each country. Despite these shared factors, unique best models were identified for each of the three countries. In Italy, maternal age and poor physical health were related to more mental health symptoms, while in the Netherlands maternal high education and unemployment were associated with mental health symptoms. In China, having more than one child, being married, and grandparental support for mothers were important protective factors lowering the risk for mental health symptoms. Moreover, high SES (mother's high education, high family income) and poor physical health were found to relate to high levels of mental health symptoms among Chinese mothers. CONCLUSIONS: These findings are important for the identification of at-risk mothers and the development of mental health promotion programs during COVID-19 and future pandemics.

The Artificial-Liver Blood-Purification System Can Effectively Improve Hypercytokinemia for COVID-19.

Since the December 2019 outbreak of coronavirus disease 2019 (COVID-19) in Wuhan, the infection has spread locally and globally resulting in a pandemic. As the numbers of confirmed diagnoses and deaths continue to rise, COVID-19 has become the focus of international public health. COVID-19 is highly contagious, and there is no effective treatment yet. New treatment strategies are urgently needed to improve the treatment success rate of severe and critically ill patients. Increasing evidence has shown that a cytokine storm plays an important role in the progression of COVID-19. The artificial-liver blood-purification system (ALS) is expected to improve the outcome of the cytokine storm. In the present study, the levels of cytokines were detected in 12 COVID-19 patients pre- and post-ALS with promising results. The present study shows promising evidence that ALS can block the cytokine storm, rapidly remove the inflammatory mediators, and hopefully, suppress the progression of the disease, thereby providing a new strategy for the clinical treatment of COVID-19.

Biochemical and antigenic characterization of the structural proteins and their post-translational modifications in purified SARS-CoV-2 virions of an inactivated vaccine candidate.

In the face of COVID-19 pandemic caused by the newly emerged SARS-CoV-2, an inactivated, Vero cell-based, whole virion vaccine candidate has been developed and entered into phase III clinical trials within six months. Biochemical and immunogenic characterization of structural proteins and their post-translational modifications in virions, the end-products of the vaccine candidate, would be essential for the quality control and process development of vaccine products and for studying the immunogenicity and pathogenesis of SARS-CoV-2. By using a panel of rabbit antisera against virions and five structural proteins together with a convalescent serum, the spike (S) glycoprotein was shown to be N-linked glycosylated, PNGase F-sensitive, endoglycosidase H-resistant and cleaved by Furin-like proteases into S1 and S2 subunits. The full-length S and S1/S2 subunits could form homodimers/trimers. The membrane (M) protein was partially N-linked glycosylated; the accessory protein 3a existed in three different forms, indicative of cleavage and dimerization. Furthermore, analysis of the antigenicity of these proteins and their post-translationally modified forms demonstrated that S protein induced the strongest antibody response in both convalescent and immunized animal sera. Interestingly, immunization with the inactivated vaccine did not elicit antibody response against the S2 subunit, whereas strong antibody response against both S1 and S2 subunits was detected in the convalescent serum. Moreover, vaccination stimulated stronger antibody response against S multimers than did the natural infection. This study revealed that the native S glycoprotein stimulated neutralizing antibodies, while bacterially-expressed S fragments did not. The study on S modifications would facilitate design of S-based anti-SARS-CoV-2 vaccines.

Risk estimation and prediction of the transmission of coronavirus disease-2019 (COVID-19) in the mainland of China excluding Hubei province.

BACKGROUND: In December 2019, an outbreak of coronavirus disease (later named as COVID-19) was identified in Wuhan, China and, later on, detected in other parts of China. Our aim is to evaluate the effectiveness of the evolution of interventions and self-protection measures, estimate the risk of partial lifting control measures and predict the epidemic trend of the virus in the mainland of China excluding Hubei province based on the published data and a novel mathematical model. METHODS: A novel COVID-19 transmission dynamic model incorporating the intervention measures implemented in China is proposed. COVID-19 daily data of the mainland of China excluding Hubei province, including the cumulative confirmed cases, the cumulative deaths, newly confirmed cases and the cumulative recovered cases between 20 January and 3 March 2020, were archived from the National Health Commission of China (NHCC). We parameterize the model by using the Markov Chain Monte Carlo (MCMC) method and estimate the control reproduction number (Rc), as well as the effective daily reproduction ratio- Re(t), of the disease transmission in the mainland of China excluding Hubei province. RESULTS: The estimation outcomes indicate that Rc is 3.36 (95% CI: 3.20-3.64) and Re(t) has dropped below 1 since 31 January 2020, which implies that the containment strategies implemented by the Chinese government in the mainland of China are indeed effective and magnificently suppressed COVID-19 transmission. Moreover, our results show that relieving personal protection too early may lead to a prolonged disease transmission period and more people would be infected, and may even cause a second wave of epidemic or outbreaks. By calculating the effective reproduction ratio, we prove that the contact rate should be kept at least less than 30% of the normal level by April, 2020. CONCLUSIONS: To ensure the pandemic ending rapidly, it is necessary to maintain the current integrated restrict interventions and self-protection measures, including travel restriction, quarantine of entry, contact tracing followed by quarantine and isolation and reduction of contact, like wearing masks, keeping social distance, etc. People should be fully aware of the real-time epidemic situation and keep sufficient personal protection until April. If all the above conditions are met, the outbreak is expected to be ended by April in the mainland of China apart from Hubei province.